tbuckley/cabot-search huggingface dataset:
Assessment of Microfinance Interventions and Intimate Partner Violence
Authors: Lao-Tzu Allan-Blitz, Rose Olson, Quang Tran
Journal: JAMA Network Open (2023)

Importance An estimated 27% of ever-partnered women aged 15 to 49 years have experienced intimate partner violence (IPV) in their lifetimes, which has been associated with a wide range of both acute and chronic illness. Poverty is thought to be a major driver of IPV, and economic empowerment programs may reduce violence. Objective To evaluate whether microfinance interventions are associated with reductions in various forms of IPV. Data Sources On August 3, 2022, PubMed, CINAHL, Embase, Web of Science, EconLit, and 5 global health databases were searched from inception. Study Selection Included studies were randomized clinical trials evaluating the effect of microfinance interventions vs control on exposure to IPV. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Data Extraction and Synthesis Authors independently assessed study eligibility, extracted prespecified data, and evaluated risk of bias using the Cochrane Risk of Bias tool. Main Outcomes and Measures Outcome measures of interest were exposure to overall IPV and 4 World Health Organization–designated IPV domains: physical, psychological and emotional, sexual, and controlling behaviors. Univariate meta-analyses using a random effects model were used to calculate the standardized mean differences (SMDs) and 95% CIs for each IPV outcome. The Grading of Recommendations Assessment, Development, and Evaluation method was used to rate the certainty of findings. Results Overall, 10 randomized clinical trials met inclusion criteria, with a total of 16 136 participants, of whom 98% identified as women, with a mean age of 28.9 years. Compared with no intervention, participation in microfinance was associated with lower rates of psychological and emotional violence (SMD, 0.87; 95% CI, 0.80-0.95; I 2 = 46%; high certainty), sexual violence (SMD, 0.76; 95% CI, 0.63-0.90; I 2 = 44%; low certainty), and controlling behaviors (SMD, 0.82; 95% CI, 0.74-0.92; I 2 = 54%; high certainty). There was no significant association with physical violence (SMD, 0.89; 95% CI, 0.76-1.04; very-low certainty). Conclusions and Relevance This systematic review and meta-analysis of microfinance interventions found a reduction in exposure to psychological and emotional IPV as well as controlling behaviors among participants receiving microfinance interventions, with high certainty evidence. Further work is needed to evaluate which types of microfinance interventions are most effective at reducing the various forms of IPV.
Comparison of Preprint Postings of Randomized Clinical Trials on COVID-19 and Corresponding Published Journal Articles
Authors: Anthony D. Bai, Yunbo Jiang, David L. Nguyen, Carson K. L. Lo, Isabella Stefanova, Kevin Guo, Frank Wang, Cindy Zhang, Kyle Sayeau, Akhil Garg, Mark Loeb
Journal: JAMA Network Open (2023)

Importance Randomized clinical trials (RCTs) on COVID-19 are increasingly being posted as preprints before publication in a scientific, peer-reviewed journal. Objective To assess time to journal publication for COVID-19 RCT preprints and to compare differences between pairs of preprints and corresponding journal articles. Evidence Review This systematic review used a meta-epidemiologic approach to conduct a literature search using the World Health Organization COVID-19 database and Embase to identify preprints published between January 1 and December 31, 2021. This review included RCTs with human participants and research questions regarding the treatment or prevention of COVID-19. For each preprint, a literature search was done to locate the corresponding journal article. Two independent reviewers read the full text, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2 tool. Time to publication was analyzed using a Cox proportional hazards regression model. Differences between preprint and journal article pairs in terms of outcomes, analyses, results, or conclusions were described. Statistical analysis was performed on October 17, 2022. Findings This study included 152 preprints. As of October 1, 2022, 119 of 152 preprints (78.3%) had been published in journals. The median time to publication was 186 days (range, 17-407 days). In a multivariable model, larger sample size and low risk of bias were associated with journal publication. With a sample size of less than 200 as the reference, sample sizes of 201 to 1000 and greater than 1000 had hazard ratios (HRs) of 1.23 (95% CI, 0.80-1.91) and 2.19 (95% CI, 1.36-3.53) for publication, respectively. With high risk of bias as the reference, medium-risk articles with some concerns for bias had an HR of 1.77 (95% CI, 1.02-3.09); those with a low risk of bias had an HR of 3.01 (95% CI, 1.71-5.30). Of the 119 published preprints, there were differences in terms of outcomes, analyses, results, or conclusions in 65 studies (54.6%). The main conclusion in the preprint contradicted the conclusion in the journal article for 2 studies (1.7%). Conclusions and Relevance These findings suggest that there is a substantial time lag from preprint posting to journal publication. Preprints with smaller sample sizes and high risk of bias were less likely to be published. Finally, although differences in terms of outcomes, analyses, results, or conclusions were observed for preprint and journal article pairs in most studies, the main conclusion remained consistent for the majority of studies.
Linking Acute Physiology to Outcomes in the ICU: Challenges and Solutions for Research
Authors: Jose Dianti, Idunn S. Morris, Martin Urner, Marcello Schmidt, George Tomlinson, Marcelo B. P. Amato, Lluis Blanch, Gordon Rubenfeld, Ewan C. Goligher
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

ICU clinicians rely on bedside physiological measurements to inform many routine clinical decisions. Because deranged physiology is usually associated with poor clinical outcomes, it is tempting to hypothesize that manipulating and intervening on physiological parameters might improve outcomes for patients. However, testing these hypotheses through mathematical models of the relationship between physiology and outcomes presents a number of important methodological challenges. These models reflect the theories of the researcher and can therefore be heavily influenced by one's assumptions and background beliefs. Model building must therefore be approached with great care and forethought, because failure to consider relevant sources of measurement error, confounding, coupling, and time dependency or failure to assess the direction of causality for associations of interest before modeling may give rise to spurious results. This paper outlines the main challenges in analyzing and interpreting these models and offers potential solutions to address these challenges.
Proteomic Predictors of Incident Diabetes: Results From the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Mary R. Rooney, Jingsha Chen, Justin B. Echouffo-Tcheugui, Keenan A. Walker, Pascal Schlosser, Aditya Surapaneni, Olive Tang, Jinyu Chen, Christie M. Ballantyne, Eric Boerwinkle, Chiadi E. Ndumele, Ryan T. Demmer, James S. Pankow, Pamela L. Lutsey, Lynne E. Wagenknecht, Yujian Liang, Xueling Sim, Rob van Dam, E. Shyong Tai, Morgan E. Grams, Elizabeth Selvin, Josef Coresh
Journal: Diabetes Care (2023)

OBJECTIVE The plasma proteome preceding diabetes can improve our understanding of diabetes pathogenesis. RESEARCH DESIGN AND METHODS In 8,923 Atherosclerosis Risk in Communities (ARIC) Study participants (aged 47–70 years, 57% women, 19% Black), we conducted discovery and internal validation for associations of 4,955 plasma proteins with incident diabetes. We externally validated results in the Singapore Multi-Ethnic Cohort (MEC) nested case-control (624 case subjects, 1,214 control subjects). We used Cox regression to discover and validate protein associations and risk-prediction models (elastic net regression with cardiometabolic risk factors and proteins) for incident diabetes. We conducted a pathway analysis and examined causality using genetic instruments. RESULTS There were 2,147 new diabetes cases over a median of 19 years. In the discovery sample (n = 6,010), 140 proteins were associated with incident diabetes after adjustment for 11 risk factors (P &amp;lt; 10−5). Internal validation (n = 2,913) showed 64 of the 140 proteins remained significant (P &amp;lt; 0.05/140). Of the 63 available proteins, 47 (75%) were validated in MEC. Novel associations with diabetes were found for 22 the 47 proteins. Prediction models (27 proteins selected by elastic net) developed in discovery had a C statistic of 0.731 in internal validation, with ΔC statistic of 0.011 (P = 0.04) beyond 13 risk factors, including fasting glucose and HbA1c. Inflammation and lipid metabolism pathways were overrepresented among the diabetes-associated proteins. Genetic instrument analyses suggested plasma SHBG, ATP1B2, and GSTA1 play causal roles in diabetes risk. CONCLUSIONS We identified 47 plasma proteins predictive of incident diabetes, established causal effects for 3 proteins, and identified diabetes-associated inflammation and lipid pathways with potential implications for diagnosis and therapy.
GIST: Molecular Profiling Suggests 2nd Therapy
Journal: Cancer Discovery (2023)

In an analysis of ctDNA from patients with advanced gastrointestinal stromal tumors, researchers found that, following imatinib therapy, patients with KIT exon 11 plus 17 and/or 18 alterations had superior progression-free survival (PFS) and overall survival (OS) when they received ripretinib as a second-line treatment compared with sunitinib; patients with KIT exon 11 plus 13 and/or 14 alterations had superior PFS and OS with sunitinib compared with ripretinib. The findings highlight the clinical value of molecular testing.
Quantification of the hepatitis B virus cccDNA: evidence-based guidelines for monitoring the key obstacle of HBV cure
Authors: Lena Allweiss, Barbara Testoni, Mei Yu, Julie Lucifora, Chunkyu Ko, Bingqian Qu, Marc Lütgehetmann, Haitao Guo, Stephan Urban, Simon P Fletcher, Ulrike Protzer, Massimo Levrero, Fabien Zoulim, Maura Dandri
Journal: Gut (2023)

A major goal of curative hepatitis B virus (HBV) treatments is the reduction or inactivation of intrahepatic viral covalently closed circular DNA (cccDNA). Hence, precise cccDNA quantification is essential in preclinical and clinical studies. Southern blot (SB) permits cccDNA visualisation but lacks sensitivity and is very laborious. Quantitative PCR (qPCR) has no such limitations but inaccurate quantification due to codetection of viral replicative intermediates (RI) can occur. The use of different samples, preservation conditions, DNA extraction, nuclease digestion methods and qPCR strategies has hindered standardisation. Within the ICE-HBV consortium, available and novel protocols for cccDNA isolation and qPCR quantification in liver tissues and cell cultures were compared in six laboratories to develop evidence-based guidance for best practices.
Combining ferroptosis induction with MDSC blockade renders primary tumours and metastases in liver sensitive to immune checkpoint blockade
Authors: Claire Conche, Fabian Finkelmeier, Marina Pešić, Adele M Nicolas, Tim W Böttger, Kilian B Kennel, Dominic Denk, Fatih Ceteci, Kathleen Mohs, Esther Engel, Özge Canli, Yasamin Dabiri, Kai-Henrik Peiffer, Stefan Zeuzem, Gabriela Salinas, Thomas Longerich, Huan Yang, Florian R Greten
Journal: Gut (2023)

Investigating the effect of ferroptosis in the tumour microenvironment to identify combinatory therapy for liver cancer treatment.Glutathione peroxidase 4 (GPx4), which is considered the master regulator of ferroptosis, was genetically altered in murine models for hepatocellular carcinoma (HCC) and colorectal cancer (CRC) to analyse the effect of ferroptosis on tumour cells and the immune tumour microenvironment. The findings served as foundation for the identification of additional targets for combine therapy with ferroptotic inducer in the treatment of HCC and liver metastasis.Surprisingly, hepatocyte-restricted GPx4 loss does not suppress hepatocellular tumourigenesis. Instead, GPx4-associated ferroptotic hepatocyte death causes a tumour suppressive immune response characterised by a CXCL10-dependent infiltration of cytotoxic CD8+ T cells that is counterbalanced by PD-L1 upregulation on tumour cells as well as by a marked HMGB1-mediated myeloid derived suppressor cell (MDSC) infiltration. Blocking PD-1 or HMGB1 unleashes T cell activation and prolongs survival of mice with Gpx4-deficient liver tumours. A triple combination of the ferroptosis inducing natural compound withaferin A, the CXCR2 inhibitor SB225002 and α-PD-1 greatly improves survival of wild-type mice with liver tumours. In contrast, the same combination does not affect tumour growth of subcutaneously grown CRC organoids, while it decreases their metastatic growth in liver.Our data highlight a context-specific ferroptosis-induced immune response that could be therapeutically exploited for the treatment of primary liver tumours and liver metastases.
Results of Phase III Randomized Trial for Use of Docetaxel as a Radiosensitizer in Patients With Head and Neck Cancer, Unsuitable for Cisplatin-Based Chemoradiation
Authors: Vijay Maruti Patil, Vanita Noronha, Nandini Menon, Ajay Singh, Sarbani Ghosh-Laskar, Ashwini Budrukkar, Atanu Bhattacharjee, Monali Swain, Vijayalakshmi Mathrudev, Kavita Nawale, Arun Balaji, Zoya Peelay, Mitali Alone, Shruti Pathak, Abhishek Mahajan, Suman Kumar, Nilendu Purandare, Archi Agarwal, Ameya Puranik, Shantanu Pendse, Monica Reddy Yallala, Harsh Sahu, Venkatesh Kapu, Sayak Dey, Jatin Choudhary, Madala Ravi Krishna, Alok Shetty, Naveen Karuvandan, Rahul Ravind, Rahul Rai, Kunal Jobanputra, Pankaj Chaturvedi, Prathamesh S. Pai, Devendra Chaukar, Sudhir Nair, Shivakumar Thiagarajan, Kumar Prabhash
Journal: Journal of Clinical Oncology (2023)

There is a lack of published literature on systemic therapeutic options in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing chemoradiation. Docetaxel was assessed as a radiosensitizer in this situation.This was a randomized phase II/III study. Adult patients (age ≥ 18 years) with LAHNSCC planned for chemoradiation and an Eastern Cooperative Oncology Group performance status of 0-2 and who were cisplatin-ineligible were randomly assigned in 1:1 to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS).The study recruited 356 patients between July 2017 and May 2021. The 2-year DFS was 30.3% (95% CI, 23.6 to 37.4) versus 42% (95% CI, 34.6 to 49.2) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.673; 95% CI, 0.521 to 0.868; P value = .002). The corresponding median overall survival (OS) was 15.3 months (95% CI, 13.1 to 22.0) and 25.5 months (95% CI, 17.6 to 32.5), respectively (log-rank P value = .035). The 2-year OS was 41.7% (95% CI, 34.1 to 49.1) versus 50.8% (95% CI, 43.1 to 58.1) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.747; 95% CI, 0.569 to 0.980; P value = .035). There was a higher incidence of grade 3 or above mucositis (22.2% v 49.7%; P < .001), odynophagia (33.5% v 52.5%; P < .001), and dysphagia (33% v 49.7%; P = .002) with the addition of docetaxel.The addition of docetaxel to radiation improved DFS and OS in cisplatin-ineligible patients with LAHNSCC.[Media: see text].
Controlling C2C12 Cytotoxicity on Liquid Metal Embedded Elastomer (LMEE)
Authors: Phillip Won, Stephen Coyle, Seung Hwan Ko, David Quinn, K. Jimmy Hsia, Philip LeDuc, Carmel Majidi
Journal: Advanced Healthcare Materials (2023)

Abstract Liquid metal embedded elastomers (LMEEs) are highly stretchable composites comprising microscopic droplets of eutectic gallium‐indium (EGaIn) liquid metal embedded in a soft rubber matrix. They have a unique combination of mechanical, electrical, and thermal properties that make them attractive for potential applications in flexible electronics, thermal management, wearable computing, and soft robotics. However, the use of LMEEs in direct contact with human tissue or organs requires an understanding of their biocompatibility and cell cytotoxicity. In this study, the cytotoxicity of C2C12 cells in contact with LMEE composites composed of EGaIn droplets embedded with a polydimethylsiloxane (PDMS) matrix is investigated. In particular, the influence of EGaIn volume ratio and shear mixing time during synthesis on cell proliferation and viability is examined. The special case of electrically‐conductive LMEE composites in which a percolating network of EGaIn droplets is created through “mechanical sintering” is also examined. This study in C2C12 cytotoxicity represents a first step in determining whether LMEE is safe for use in implantable biomedical devices and biohybrid systems.
Phase I Study of Single-Agent Anti–Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates
Authors: Julie R. Brahmer, Charles G. Drake, Ira Wollner, John D. Powderly, Joel Picus, William H. Sharfman, Elizabeth Stankevich, Alice Pons, Theresa M. Salay, Tracee L. McMiller, Marta M. Gilson, Changyu Wang, Mark Selby, Janis M. Taube, Robert Anders, Lieping Chen, Alan J. Korman, Drew M. Pardoll, Israel Lowy, Suzanne L. Topalian
Journal: Journal of Clinical Oncology (2023)

Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti-PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates.
SGLT2 Inhibitors: The Sweet Success for Kidneys
Authors: Atit Dharia, Abid Khan, Vikas S. Sridhar, David Z.I. Cherney
Journal: Annual Review of Medicine (2023)

Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) were originally developed as antidiabetic agents, with cardiovascular (CV) outcome trials demonstrating improved CV outcomes in patients with type 2 diabetes mellitus (T2D). Secondary analyses of CV outcome trials and later dedicated kidney outcome trials consistently reported improved kidney-related outcomes independent of T2D status and across a range of kidney function and albuminuria. Importantly, SGLT2 inhibitors are generally safe and well tolerated, with clinical trials and real-world analyses demonstrating a decrease in the risk of acute kidney injury. The kidney protective effects of SGLT2 inhibitors generally extend across different members of the class, possibly on the basis of hemodynamic, metabolic, anti-inflammatory, and antifibrotic mechanisms. In this review, we summarize the effects of SGLT2 inhibitors on kidney outcomes in diverse patient populations.
Maternal Mortality in the United States: Trends and Opportunities for Prevention
Authors: Siwen Wang, Kathryn M. Rexrode, Andrea A. Florio, Janet W. Rich-Edwards, Jorge E. Chavarro
Journal: Annual Review of Medicine (2023)

Maternal mortality is unusually high in the United States compared to other wealthy nations and is characterized by major disparities in race/ethnicity, geography, and socioeconomic factors. Similar to other developed nations, the United States has seen a shift in the underlying causes of pregnancy-related death, with a relative increase in mortality resulting from diseases of the cardiovascular system and preexisting medical conditions. Improved continuity of care aimed at identifying reproductive-age women with preexisting conditions that may heighten the risk of maternal death, preconception management of risk factors for major adverse pregnancy outcomes, and primary care visits within the first year after delivery may offer opportunities to address gaps in medical care contributing to the unacceptable rates of maternal mortality in the United States.
New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics
Authors: Ania M. Jastreboff, Robert F. Kushner
Journal: Annual Review of Medicine (2023)

Nearly half of Americans are projected to have obesity by 2030, underscoring the pressing need for effective treatments. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) represent the first agents in a rapidly evolving, highly promising landscape of nascent hormone-based obesity therapeutics. With the understanding of the neurobiology of obesity rapidly expanding, these emerging entero-endocrine and endo-pancreatic agents combined or coformulated with GLP-1 RAs herald a new era of targeted, mechanism-based treatment of obesity. This article reviews GLP-1 RAs in the treatment of obesity and previews the imminent future of nutrient-stimulated hormone-based anti-obesity therapeutics.
Chronic Neuromuscular Respiratory Failure and Home Assisted Ventilation
Authors: Hugo Carmona, Andrew D. Graustein, Joshua O. Benditt
Journal: Annual Review of Medicine (2023)

Chronic respiratory failure is a common, important complication of many types of neuromuscular and chest wall disorders. While the pathophysiology of each disease may be different, these disorders can variably affect all muscles involved in breathing, including inspiratory, expiratory, and bulbar muscles, ultimately leading to chronic respiratory failure and hypoventilation. The use of home assisted ventilation through noninvasive interfaces aims to improve the symptoms of hypoventilation, improve sleep quality, and, when possible, improve mortality. An increasing variety of interfaces has allowed for improved comfort and compliance. In a minority of scenarios, noninvasive ventilation is either not appropriate or no longer effective due to disease progression, and a transition to tracheal ventilation should be considered.
Use of Race in Kidney Function Estimation: Lessons Learned and the Path Toward Health Justice
Authors: Dinushika Mohottige, Opeyemi Olabisi, L. Ebony Boulware
Journal: Annual Review of Medicine (2023)

In 2020, the nephrology community formally interrogated long-standing race-based clinical algorithms used in the field, including the kidney function estimation equations. A comprehensive understanding of the history of kidney function estimation and racial essentialism is necessary to understand underpinnings of the incorporation of a Black race coefficient into prior equations. We provide a review of this history, as well as the considerations used to develop race-free equations that are a guidepost for a more equity-oriented, scientifically rigorous future for kidney function estimation and other clinical algorithms and processes in which race may be embedded as a variable.
Exome/Genome Sequencing in Undiagnosed Syndromes
Authors: Jennifer A. Sullivan, Kelly Schoch, Rebecca C. Spillmann, Vandana Shashi
Journal: Annual Review of Medicine (2023)

Exome sequencing (ES) and genome sequencing (GS) have radically transformed the diagnostic approach to undiagnosed rare/ultrarare Mendelian diseases. Next-generation sequencing (NGS), the technology integral for ES, GS, and most large (100+) gene panels, has enabled previously unimaginable diagnoses, changes in medical management, new treatments, and accurate reproductive risk assessments for patients, as well as new disease gene discoveries. Yet, challenges remain, as most individuals remain undiagnosed with current NGS. Improved NGS technology has resulted in long-read sequencing, which may resolve diagnoses in some patients who do not obtain a diagnosis with current short-read ES and GS, but its effectiveness is unclear, and it is expensive. Other challenges that persist include the resolution of variants of uncertain significance, the urgent need for patients with ultrarare disorders to have access to therapeutics, the need for equity in patient access to NGS-based testing, and the study of ethical concerns. However, the outlook for undiagnosed disease resolution is bright, due to continual advancements in the field.